Clinical Oral Investigations

https://doi.org/10.1007/s00784-019-03023-7

ORIGINAL ARTICLE

Autistic patients: a retrospective study on their dental needs

and the behavioural approach
Francesca Mangione 1,2 & Fadi Bdeoui 3 & Aude Monnier-Da Costa 3 & Elisabeth Dursun 3,4

Received: 6 June 2018 / Accepted: 11 July 2019

# Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract
Introduction Autism spectrum disorder (ASD) is a lifelong heterogeneous psychiatric disorder that represents a challenge for
dentists. The aim of this retrospective study was to analyse ASD patients’ dental needs and to investigate key factors influencing
the behavioural management.
Materials and methods One hundred eighteen ASD subjects (levels 2 and 3 of the DSM-5), adults and children, treated at
university dental hospital, were included. For each of them, an index card was created to record general and medical information,
dental care progress and treatment management. Data were analysed to characterize this specific population in terms of dental
needs, technical approach and follow-up. The relationships between care approach and age (ANOVA test), care approach and
concomitant pathologies as well as care approach and required treatment (chi-square test) were evaluated.
Results Almost all patients required oral care. No treatment could be provided under conscious conditions. Oral premedication
and/or nitrous oxide/oxygen inhalation was significantly more efficient in children and allowed conservative procedures. In
adults, general anaesthesia was significantly more employed. Few patients were followed up over a long period.
Conclusions The variety of autism spectrum disorders complicates the statement of guidelines for dental care. The development
of the collaboration between psychiatrics and dentists emerges as a key factor to improve the quality and the success of oral
outpatient treatment.
Clinical relevance Oral premedication and/or nitrous oxide/oxygen inhalation at high dose represented a good way to carry out
conservative dental cares, with a significant efficiency in children. Nevertheless, in a considerable number of ASD patients,
especially in adults, general anaesthesia could not be avoided.

Keywords Autism . Autism spectrum disorder . Dentistry . Behavior management . Sedation

Introduction childhood. According to the fifth edition of Diagnostic and

Statistical Manual of Mental Disorders (DSM-5), ASD is
Autism spectrum disorder (ASD) is a heterogeneous characterized by persistent deficits in social communication
neurodevelopmental disorder, occurring in infancy or early and social interaction, as well as restricted, repetitive patterns
of behaviour, interests or activities. These symptoms must be
present in the early developmental period and cause clinically
* Elisabeth Dursun
[email protected] significant impairment in social, occupational or other impor-
tant areas of current functioning [1]. Although the aetiology is
1
Oral Pathology and Surgery Department & Orofacial Pathologies, still unknown, several hypotheses have been proposed: neu-
Imaging and Biotherapies (EA2496), Faculty of Dental Surgery, ropsychological, structural or functional alterations [2].
Paris Descartes University, 1 rue Maurice Arnoux,
Genetic and environmental factors, such as neonatal or peri-
92120 Montrouge, France
2
natal complications, viral infections, metabolic imbalances
Oral Pathology and Surgery Department, Henri Mondor Hospital, 2
and exposure to chemicals, may also be involved [3, 4]. The
rue Gustave Eiffel, 94000 Créteil, France
3
prevalence seems to be risen and is currently estimated at
Paediatric Dentistry Department, Henri Mondor Hospital, 2 rue
around 1% [5, 6]. This increase will necessarily result in larger
Gustave Eiffel, 94000 Créteil, France
4
number of ASD patients seen by all healthcare providers.
Paediatric Dentistry Department & Innovative Dental Materials and
ASD patient’s attitudes vary considerably, from care coop-
Interfaces Research Unit (EA4462), Faculty of Dental Surgery, Paris
Descartes University, 1 rue Maurice Arnoux, eration to impossibility to perform an oral examination.
92120 Montrouge, France Difficulties in verbal and nonverbal communication, fear
 Clin Oral Invest

and anxiety, obsessive resistance to changes in routine and (supragingival tartar), gingivitis (generalized gingival inflam-
sensory abnormalities [7] are regularly presented in ASD pa- mation, i.e. gingival overgrowth and/or bleeding) or periodon-
tients. Additionally, when in the dental office, the unfamiliar titis (soft tissues and bone loss); traumas (dental and alveolar
environment, dental operatory light, instruments noises and bone traumas); tooth infections (periapical periodontitis and
taste of dental materials can be perceived as aggressive abscesses) and malocclusions (mild to severe dental and/or
and may trigger patients’ anxiety [8–10]. In fact, thera- alveolar malocclusions); (2) performed the following treat-
peutic and even diagnostic procedures often require sed- ments: sealants; fluoride varnish applications; supragingival
ative premedication or general anaesthesia. Moreover, medi- scaling and/or subgingival root planning; radiographies; tooth
cations such as psychoactive drugs or anticonvulsants and restorations (direct fillings without pulp involvement); end-
multiple medical issues frequently associated strongly com- odontic treatments (pulpotomies and root canal treatments)
plicate the management of these patients. and extractions; (3) care approach: consciousness; oral
Little has been published on the dental health of ASD pa- premedication; nitrous oxide/oxygen inhalation and oral
tients. These few reports available in the literature focused on the premedication in association with nitrous oxide/oxygen inha-
oral health status [11, 12], the unmet dental need [13], as well as lation and general anaesthesia.
the behavioural approach [14, 15] and the role of educators and
healthcare providers [16]. To our knowledge, no studies have Data analysis
already described how these specific patients are treated, accord-
ing to their general medical conditions and their dental needs. Data were input in a spreadsheet and analysed. Descriptive
The aim of this retrospective study was to analyse the den- statistics was performed to provide the picture of the oral health
tal needs of patients referred to or attending a university dental needs in ASD patients, according to the three groups: children
clinic. A second aim was to investigate key factors influencing (4 to 12 years old), adolescents (13 to 17 years old) and adults
the behavioural management, by analysing the influence of (18 to 53 years old). A one-way ANOVAwas used to determine
the age, the concomitant pathologies and the required treat- whether there was a relation of dependence between the age
ment on the care approach. and the type of care approach. The chi-square tests were used to
determine the association between the presence of concomitant
pathologies and the care approach, as well as the association
Materials and methods between the required treatment (restorative care, extraction,
restorative care and extraction) and the care approach
Subjects (p < 0.05). All calculations and tests were performed on Excel
(Microsoft Office®) and PAWS statistics 18 (SPSS, USA).
One hundred eighteen ASD patients (age range of 4–53 years
old), diagnosed with the levels 2 or 3 of the DSM-5 (respec- Ethics
tively defined as requiring substantial and very substantial
support), were included in this retrospective study. All of them This retrospective study was carried out by medical record
were treated in the special dental care department of the Henri review. Ethical approval was granted by the departmental
Mondor-Albert Chenevier University Hospital Group ethics committee of the Henri Mondor-Albert Chenevier
(Créteil, France), from 2004 to 2015. University Hospital Group.

Data collection
Results
For each of them, an index card was created to record personal
and medical data and oral treatments. In the card, 4 sections Patients’ characteristics and dental needs
were distinguished: general information, medical information,
dental care progress and treatment management. The subjects’ characteristics are summarized in Table 1. One
In the first section, demographic characteristics including hundred eighteen patients, with 89 males and 29 females,
surname, first name, sex, birthday, zip code and file number were involved in this study. The mean age was 23.3 years
were recorded. In the second section, data concerning height, old (ranging from 4 to 53 years old). The average number of
weight, concomitant pathologies, medications and oral reper- appointments per patient was 4.1, and regardless of general
cussions of ASD (i.e. bruxism and self-injury) were noted; in anaesthesia, the average number of care sessions was 1.6. The
the third section, date of first and last appointments as well as mean follow-up time was 1.5 years. Only 29.7% of patients
number of appointments and care sessions were report- were followed up for more than 2 years, 33.1% came only
ed. The last section reported: (1) oral and dental pathologies, once and 4.2% missed at least 1 appointment. 25.4% of the
such as tooth decays (carious lesions with cavity); calculus overall patients lived outside the hospital district.
Clin Oral Invest

Table 1 Patients’ general

information Number of patients 118
Average age 23 years old (4 to 53 years old)
Number of children (4 to 12 years old) 54
Number of adolescents (13 to 17 years old) 29
Number of adults (18 to 53 years old) 35
Sex 89 males, 29 females
Patients living outside hospital district 25.4% (30/118)
Average follow-up period 1.5 years
Follow-up > 2 years—29.7% (35/118)
Average number of appointments 4.1
Only 1 appointment—33.1% (39/118)
Average number of care sessions 1.6
Missed appointment ≥ 1—4.2% (5/118)
All percentages correspond to ratio between the number patients with the characteristic and the total number
of patients

Tables 2, 3 and 4 describe medical information, oral and adolescents—10.3%), while some adults needed not only
dental pathologies and treatment management, respectively, supragingival scaling (8.6%) but also additional subgingival
for children, adolescents and adults. root planning (14.3%).
Almost a quarter of children (22.4%) had associated pa- For all patients, except for clinical examination, no cares
thologies, whereas half adolescents (44.8%) and adults could be provided under conscious conditions. Various care
(51.4%) were affected. The most encountered pathologies approaches could be applied on the same patient. In children,
were epilepsy, in particular in adults (22.9%), and then asthma there were more treatments under nitrous oxide/oxygen inha-
mostly in adolescents (10.3%). Besides, almost all adults were lation with (46.3%) or without oral premedication (31.5%).
undergoing medications (97.1%), whereas only a smaller Adolescents and even more adults more often required nitrous
number of children (16.7%) and adolescents (34.5%) did. oxide/oxygen inhalation with oral premedication (respectively
Adults took more neuroleptic drugs and anxiolytics than 41.4% and 37.1%) and general anaesthesia (respectively
younger patients. 48.3% and 57.1%). Table 5 summarizes the distribution of
Almost all patients presented oral and dental pathologies at age, concomitant pathologies and required treatment among
first appointment. In particular, 24.1% adolescents and the five groups of care approach and the statistical analysis.
28.6% adults presented malocclusions, against only The distribution of the age significantly differed in the various
7.4% of children. Regarding tooth infections, 24.1% of care approaches (ANOVA test, p = 0.0016): the adults were
children, 13.8% of adolescents and 28.6% of adults statistically more often treated under general anaesthesia
were affected, with a higher number of primary teeth (mean age 24.5 years old), and children were statistically more
in children. Children showed more traumas (14.8%) often treated under nitrous oxide/oxygen inhalation (mean age
than older patients (adolescents—6.9%; adults—2.9%), 7.0 years old). Besides, oral premedication in association with
while adults suffered more frequently from bruxism nitrous oxide/oxygen inhalation was also significantly used in
(34.3%), compared with children (11.1%) and adoles- adults (mean age 23.5 years old). The presence of concomitant
cents (10.3%). Self-injuries were similarly encountered pathologies was not significantly associated with the type of
in the three groups. approach (chi-square test, p = 0.37). However, it can be noted
that patients treated under oral premedication combined with
Treatment, management and follow-up nitrous oxide/oxygen inhalation or under general anaesthesia
had more frequently concomitant pathologies (respectively
Sealants were only applied in children (9.3%). Restorative 12.7% and 11.0%) compared with those treated under oral
treatments were often performed (children—31.5%; adoles- premedication only or nitrous oxide/oxygen inhalation only
cents—27.6%; adults—42.9%). Endodontic treatments were (0.85% for both). The required therapies (restorative
more frequently carried out in children (14.8%), compared treatment, endodontic treatment and extraction) were
with adolescents (3.4%) and adults (2.9%). Tooth extractions significantly associated with the type of approach (chi-
were numerous in all age groups (children—57.4%; adoles- square test, p = 0.0024). In fact, patients needing more
cents—34.5.9%; adults—45.7%). Finally, young patients invasive procedures (i.e. tooth extractions) were statisti-
benefited from supragingival scaling (children—20.4%; cally more frequently treated under general anaesthesia
 Clin Oral Invest

Table 2 Children’s characteristic distribution: medical information, oral and dental pathologies and treatment management

Medical information Patients with concomitant pathologies 22.2% (12/54)

Most encountered pathologies 11.1% (6/54) Epilepsy
3.7% (2/54) Asthma
3.7% (2/54) Trisomy 21
Patients under medications 16.7% (9/54)
Medications 7.4% (4/54) Neuroleptic drugs
11.1% (6/54) Antiepileptic drugs
1.9% (1/54) Anxiolytics
0.0% (0/54) Antidepressants
Patients under medications 11.1% (6/54) Bruxism
3.7% (2/54) Self-injury
Oral and dental pathologies Patients with oral and dental pathologies 90.7% (49/54)
at first appointment
Patients requiring mandatory orthodontic 7.4% (4/54)
treatment
Patients with tooth infections 18.5% (10/54) Primary teeth
5.6% (3/54) Permanent teeth
24.1% (13/54) Total
Patients with dental traumas 14.8% (8/54)
Treatment management Performed treatments 9.3% (5/54) Sealant
13.0% (7/54) Single tooth restorative treatment
18.5% (10/54) Multiple restorative treatments
31.5% (17/54) Total
7.4% (4/54) Single tooth endodontic treatment*
7.4% (4/54) Multiple endodontic treatments*
14.8% (8/54) Total
22.2% (12/54) Single tooth extraction**
35.2% (19/54) Multiple extractions***
57.4% (31/54) Total
20.4% (12/54) Supragingival scaling
0.0% (0/54) Subgingival root planning
Care approach 0.0% (0/54) Conscious conditions
13.0% (7/54) Oral premedication
31.5% (17/54) Nitrous oxide/oxygen inhalation
46.3% (25/54) Oral premedication + nitrous oxide/oxygen
inhalation
9.3% (5/54) General anaesthesia

All percentages correspond to ratio between the number of patients with the characteristic and the total number of patients
*All endodontic treatments were pulpotomies on primary teeth **including one permanent molar and ***including 2 permanent molars

(23.7%) compared with the other care approaches, in result in patients’ limited collaboration to dental procedures.
particular compared with patients treated under oral Thus, ASD patients represent a real challenge for dentists.
premedication (0.8%) and patients treated under nitrous
oxide/oxygen inhalation (6.8%). Subjects

Literature on autism mostly focused on paediatric populations,

Discussion but little has been published on adults. This study analysed a
large sample of ASD patients, between the ages of 4 and
The ASD is an emerging public health issue, due to its increas- 53 years. Males were three times more frequent than females,
ing prevalence over the last decades. The complexity and the corroborating with prior literature [17, 18]. A lot of patients
variety of the clinical manifestations, related to this disorder, suffered from concomitant pathologies and primarily of
Clin Oral Invest

Table 3 Adolescents’ characteristics distribution: medical information, oral and dental pathologies and treatments management

Medical information Patients with concomitant pathologies 44.8% (13/29)

Most encountered pathologies 13.8% (4/29) Epilepsy
10.3% (3/29) Asthma
3.4% (1/29) Trisomy 21
Patients under medications 34.5% (10/29)
Medications 17.2% (5/29) Neuroleptic drugs
13.8% (4/29) Antiepileptic drugs
3.4% (1/29) Anxiolytics
0.0% (0/29) Antidepressants
Most encountered ASD oral repercussions 10.3% (3/29) Bruxism
6.9% (2/29) Self-injury
Oral and dental pathologies Patients with oral and dental pathologies 93.1% (27/29)
at first appointment
Patients requiring mandatory orthodontic 24.1% (7/29)
treatment
Patients with tooth infections 0.0% (0/29) Primary teeth
13.8% (4/29) Permanent teeth
13.8% (4/29) Total
Patients with dental traumas 6.9% (2/29)
Treatment management Performed treatments 6.9% (2/29) Single tooth restorative treatment
20.7% (6/29) Multiple restorative treatments
27.6% (8/29) Total
3.4% (1/29) Single tooth endodontic treatment*
0.0% (0/29) Multiple endodontic treatments
3.4% (1/29) Total
13.8% (4/29) Single tooth extraction
20.7% (6/29) Multiple extractions**
34.5% (10/29) Total
10.3% (3/29) Supragingival scaling
3.4% (1/29) Subgingival root planning
Care approach 0.0% (0/29) Conscious conditions
10.3% (3/29) Oral premedication
0.0% (0/29) Nitrous oxide/oxygen inhalation
41.4% (12/29) Oral premedication + nitrous oxide/oxygen
inhalation
48.3% (14/29) General anaesthesia

All percentages correspond to ratio between the number of patients with the characteristic and the total number of patients
*The only endodontic treatment was a pulpotomy on permanent molar **including 3 patients with primary tooth extractions

epilepsy [19] (between 11.1 and 22.9% of patients, compared population. In fact, in this study, self-injuries are more fre-
with 0.64% in general population [20]) and were regularly quent than in general population (between 2.9 and 6.9%, com-
taking one or more medications (between 16.7% in children pared with 0.0% [22, 23]), while bruxism is similar (11.1% of
and 97.1% in adults), in agreement with other studies [21]. children, compared with 3.5 to 40.6% [24] in general paedi-
Besides, neuroleptic drugs and anxiolytics were more taken atric population and 34.3% of adults compared with 31.4% in
by adults than younger patients, because most of them are not general population [25]), which is in accordance with previous
recommended in paediatric age. The combination of multiple literature [22].
medications complicates the choice of oral premedication, if
needed. In fact, tolerance and inefficiency of sedative agents Oral and dental pathologies and required therapies
could require higher dose than usually recommended.
Besides, the prevalence of oral repercussions in these pa- Almost all patients (between 90.7 and 94.1%) presented oral
tients does not always match the prevalence in general or dental pathologies at the first appointment, and a significant
 Clin Oral Invest

Table 4 Adults’ characteristic distribution: medical information, oral and dental pathologies and treatment management

Medical information Patients with concomitant pathologies 51.4% (18/35)

Most encountered pathologies 22.9% (8/35) Epilepsy
0.0% (0/35) Asthma
2.9% (1/35) Trisomy 21
Patients under medications 97.1% (34/35)
Medications 60.0% (21/35) Neuroleptic drugs
37.1% (13/35) Antiepileptic drugs
17.1% (6/35) Anxiolytics
8.6% (3/35) Antidepressants
Most encountered ASD oral repercussions 34.3% (12/35) Bruxism
2.9% (1/35) Self-injury
Oral and dental pathologies Patients with oral and dental pathologies at 94.3% (33/35)
first appointment
Patients requiring mandatory orthodontic treatment 28.6% (10/35)
Patients with tooth infections 28.6% (10/35)
Patients with dental traumas 2.9% (1/35)
Treatment management Performed treatments 17.1% (6/35) Single tooth restorative treatment
25.7% (9/35) Multiple restorative treatments
42.9% (12/35) Total
0.0% (0/35) Single tooth endodontic treatment
2.9% (1/35) Multiple endodontic treatments*
2.9% (1/35) Total
22.9% (8/35) Single tooth extraction
22.9% (8/35) Multiple extractions
45.7% (16/35) Total
8.6% (3/35) Supragingival scaling
14.3% (5/35) Subgingival root planning
Care approach 0.0% (0/35) Conscious conditions
5.7% (2/35) Oral premedication
0.0% (0/35) Nitrous oxide/oxygen inhalation
37.1% (13/35) Oral premedication + nitrous oxide/oxygen
inhalation
57.1% (20/35) General anaesthesia

All percentages correspond to ratio between the number of patients with the characteristic and the total number of patients *including
one first permanent molar

number of them were affected by tooth infections (between oral hygiene is difficult for ASD patients, which leads to the
13.8 and 28.6%). The pathologies were more often clinically development of carious and periodontal diseases. The
diagnosed. In fact, radiographies were difficult or impossible xerostomic effect induced by certain medications taken also
to perform, because the immobility of the patients could rarely contributes to caries susceptibility.
be achieved. Moreover, communication impairment and hyposensitivity
Even though there were considerable variations between to pain could also result in fewer and sparse dental visits.
regions, countries and age, age-standardized prevalence of Severity of dental pathologies is also related to the difficulty
caries is much lower in general population (8.8% and 35.4% or even to the lack of follow-up of these patients. In the pre-
for primary and permanent teeth, respectively) [26]. In addi- sented sample, the mean follow-up time was 1.5 years and a
tion, between 2.9 and 14.8% suffered from dental traumas, lot of patients (33.1%) only came once. Difficulties in care
compared with 4.5% in general population [27]. Yet, between access, due to long-duration procedures and important dis-
7.4 and 28.6% presented severe malocclusions that should tance from the hospital, could explain these results [29].
require mandatory orthodontic treatment, similar to general Overall, a third of patients received restorative treatments: in
population (15.0 to 27.0%) [28]. These data highlight the im- children, primary teeth were more involved (18.5% compared
portance of oral healthcare need. In fact, maintaining good with 5.6% of permanent teeth). Endodontic treatments were
Clin Oral Invest

Table 5 Care approach according to age, concomitant pathologies and required treatment among overall population

Age Concomitant pathologies Required treatment

Mean (±SD) p value % of patients p value % of patients p value

(ANOVA test) (number of (Χ2 test) (number of patients) (Χ2 test)
patients) with P requiring R, ET and E

Care approach Conscious condition – 0.0016 – 0.38 – 0.0038

Oral premedication 18.3 (±13.0) P 0.85% (1/118) R 6.8% (8/118)
ET 0.8% (1/118)
E 0.8% (1/118)
Nitrous oxide/oxygen 7.0 (±0.9) P 0.85% (1/118) R 2.5% (3/118)
inhalation ET 1.7% (2/118)
E 6.8% (8/118)
Oral premedication + nitrous 23.5 (±14.9) P 12.7% (15/118) R 11.0% (13/118)
oxide/oxygen inhalation ET 4.2% (5/118)
E 16.9% (20/118)
General anaesthesia 24.5 (±10.4) P 11.0% (13/118) R 11.0% (13/118)
ET 1.7% (2/118)
E 23.7% (28/118)

P presence of at least one concomitant pathology, R restorative treatment, ET endodontic treatment (pulpotomy or root canal treatment),
E tooth extraction

more frequently reported in children, but they consisted only complexity required for primary teeth care and by the more
in pulpotomies on primary teeth. In adults, only one patient successful effect of pharmacological agents in children [30].
received multiple root canal treatments, and only one perma- However, to achieve a satisfying level of sedation, combina-
nent molar had a root canal treatment. In fact, such a complex tion of several drugs was often necessary as well as higher and
and time-consuming procedure requires compliance, which is more prolonged exposure to nitrous oxide. On the contrary, in
difficult to obtain in these patients. Permanent tooth extrac- adults, the more complex clinical picture and the more inva-
tions were numerous and often multiple. In fact, there was a sive nature of required dental cares significantly more often
high number of dental infections, and it is difficult to perform demanded, a general anaesthesia approach.
root canal treatments under nitrous oxide/oxygen inhalation or Even though it is known that behavioural techniques help
under general anaesthesia. No teeth were extracted for ortho- the management of noncompliant patients, conventional be-
dontic reasons. Prosthodontic treatments were often required, havioural techniques, such as tell-show-do, positive re-
but they were impossible to implement. inforcement and nonverbal communication generally fail
Even though all patients and/or their family received oral with autistic patients. TEACCH Autism Program, Picture
hygiene and nutritional instructions at the first appointment, Exchange Communication System (PECS) [31] and Applied
oral health prevention should be enhanced in order to avoid Behaviour Analysis (ABA) seem to facilitate preventive and
such invasive procedures, frequently requiring a specific ap- dental treatment [32–34]. These strategies could improve the
proach. In fact, few sealants were performed, and fluoride compliance and emerge as promising approaches, in synergy or
varnish was only applied for permanent teeth, when the as an alternative to the sedation and even to the general sedation.
compliance was sufficient.
Multidisciplinary approach
Care approach
Educational and behavioural approaches may improve success in
In this study, no dental care was performed under conscious dental care [35]. Comprehensive medical care relies on a multi-
conditions, and at least oral premedication and/or nitrous disciplinary team. General practitioners or paediatricians gener-
oxide/oxygen inhalation were used. Thanks to sedative tech- ally diagnosing autism should refer those patients to different
niques allowing repeated sessions and avoiding tooth extrac- specialists. The dentist should be involved early to provide oral
tions, many patients could benefit from conservative cares, as prevention and avoid invasive dental treatments, always hard to
restorative treatment and dental scaling. achieve. Special educators and dieticians should also promote
This kind of approach was significantly more employed in oral hygiene and dietary habits. Psychiatrics and psycholo-
children; this could be explained by the lower technical gists, responsible for individual behaviour management,
 Clin Oral Invest

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Conflict of interest The authors declare that they have no conflict of
and therapeutic behavioral approaches to providing dental care for
interest.
patients with autism spectrum disorder. Spec Care Dentist 35:105–
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Ethical approval All procedures performed in studies involving human 16. Murshid EZ (2015) Dental knowledge of educators and healthcare
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tional and/or national research committee and with the 1964 Helsinki Saudi Med J 36:1477–1485. https://doi.org/10.15537/smj.2015.12.
declaration and its later amendments or comparable ethical standards. 12622
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disorders. Res Autism Spectr Disord 8:143–146. https://doi.org/10.
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